Metal-Free [2 + 2]-Photocycloaddition of (Z)‑4-Aryliden-5(4H)‑Oxazolones as Straightforward Synthesis of 1,3-Diaminotruxillic Acid Precursors: Synthetic Scope and Mechanistic Studies

The direct [2 + 2]-photocycloaddition of (Z)-2-phenyl-4-aryliden-5­(4H)-oxazolones 1 to give 1,3-diaminotruxillic cyclobutane derivatives 2 in very good yields (75–100%) is reported. The reaction takes place by irradiation of CH2Cl2 solutions of 1 with blue light (465 nm) provided by light-emitting diode (LED) lamps of low power (around 1 W) for 72 h. Four isomers of the 1,3-diaminotruxillic cyclobutanes 2 were obtained; all of them fully characterized by a combination of nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction analysis. The reaction shows a certain selectivity, since one of the isomers (the epsilon) is obtained preferentially, and works for electron-releasing and electron-withdrawing substituents at the arylidene ring. A novel setup is presented for the in-line monitoring of the continuous flow photoassisted synthesis of the cyclobutane derivatives 2 by NMR spectroscopy, with the microreactor dramatically reducing reaction times to only 30 min with clear product distribution of up to four isomers. The mechanism of this [2 + 2]-photocycloaddition has been calculated by density functional theory (DFT) methods, explaining all experimental findings. The reaction takes place through a stepwise formation of two new C–C bonds through a transient diradical singlet intermediate. The isomeric distribution of the final products is not due to equilibration processes but instead reflects the kinetic preference during the rate limiting C–C bond formation step.